Nanoassembly of spider silk protein mediated by intrinsically disordered regions.

Spider silk is the self-assembling product of silk proteins each containing multiple repeating units. Each repeating unit is entirely intrinsically disordered or contains a small disordered domain. The role of the disordered domain/unit in conferring silk protein storage and self-assembly is not fully understood yet. Here, we used biophysical and biochemical techniques to investigate the self-assembly of a miniature version of a minor ampullate spidroin (denoted as miniMiSp). miniMiSp consists of two identical intrinsically disordered domains, one folded repetitive domain, and two folded terminal domains. Our data indicated that miniMiSp self-assembles into oligomers and further into liquid droplets. The oligomerization is attributed to the aggregation-prone property of both the disordered domains and the folded repetitive domain. Our results support the model of micellar structure for silk proteins at high protein concentrations. The disordered domain is indispensable for liquid droplet formation via liquid-liquid phase separation, and tyrosine residues located in the disordered domain make dominant contributions to stability of the liquid droplets. As the same tyrosine residues are also critical to fibrillation, the liquid droplets are likely an intermediate state between the solution state and the fiber state. Additionally, the terminal domains contribute to the pH- and salt-dependent self-assembly properties.

Unified Cross-Structural Motion Retargeting for Humanoid Characters.

Motion retargeting for animation characters has potential applications in fields such as animation production and virtual reality. However, current methods either assume that the source and target characters have the same skeletal structure, or require designing and training specific model architectures for each structure. In this paper, we aim to address the challenge of motion retargeting across previously unseen skeletal structures with a unified dynamic graph network. The proposed approach utilizes a dynamic graph transformation module to dynamically transfer latent motion features to different structures. We also take into consideration for intricate hand movements and model both torso and hand joints as graphs in a unified manner for whole-body motion retargeting. Our model allows the use of motion data from different structures to train a unified model and learns cross-structural motion retargeting in an unsupervised manner with unpaired data. Experimental results demonstrate the superiority of the proposed method in terms of data efficiency and performance on both seen and unseen structures.

Construction and verification of a histone deacetylases-related prognostic signature model for colon cancer.

Histone deacetylases (HDACs) contribute significantly to the initiation, progression, and prognosis of colorectal adenocarcinoma (COAD). Additionally, HDACs regulate the tumor microenvironment, immune escape, and tumor stem cells, and are closely linked to COAD prognosis. We developed a prognostic model for COAD that incorporates HDACs to evaluate their specific roles. The COAD dataset containing clinical and mutation data was collected using the TCGA and GEO databases to obtain genes associated with HDAC. LASSO analysis and univariate and multivariate Cox regression analysis were used to determine the presence of prognostic genes. Multivariate Cox analysis was also used to determine risk scores for HDAC-related features. Furthermore, genomic alterations, immune infiltration, and drug response were compared between high- and low-risk groups. Cellular experiments validated the potential regulatory role of BRD3 on COAD proliferation, migration, and apoptosis. The median risk scores, calculated based on the characteristics, demonstrated a more significant prognostic improvement in patients in the low-risk group. Furthermore, HDAC-related features were identified as important independent prognostic factors for patients with COAD. Additionally, genomic mutation status, immune infiltration, and function, as well as response to immunotherapy and chemotherapy, were found to be associated with risk scores. Subgroup analyses indicate that anti-PD-1 therapy may be beneficial for patients in the low-risk group. Additionally, a decrease in risk score was associated with a decrease in immune infiltration. Finally, HCT116 and HT29 cells exhibited inhibition of BRD3 gene proliferation and migration, as well as promotion of apoptosis. In patients with COAD, HDAC-related characteristics may be useful in predicting survival and selecting treatment.

The soybean lecithin-cyclodextrin-vitamin E complex nanoparticles stabilized Pickering emulsions for the delivery of ß-carotene: Physicochemical properties and in vitro digestion.

In this work, soybean lecithin (LC) was used to modify ß-cyclodextrin (ß-CD) with hydrophobic fat chains to become amphiphilic (LC-CD), and vitamin E (VE) was encapsulated in former modified ß-CD complexes (LC-CD-VE), the new Pickering emulsions stabilized by LC-CD-VE and LC-CD complexes for the delivery of ß-carotene (BC) were created. The surface tension, contact angle, zeta potential, and particle size were used to assess the changes in complexes nanoparticles at various pH values. Furthermore, LC-CD-VE has more promise as Pickering emulsion stabilizer than LC-CD because of the smaller particle size (271.11 nm), proper contact angle (58.02°), and lower surface tension (42.49 mN/m). The interactions between ß-cyclodextrin, soybean lecithin, and vitamin E were confirmed using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and thermogravimetric analysis (TGA). The durability of Pickering emulsions was examined at various volume fractions of the oil phase and concentrations of nanoparticles. Compared to the emulsion stabilized by LC-CD, the one stabilized by LC-CD-VE showed superior storage stability. Moreover, for the delivery of BC, Pickering emulsions stabilized by LC-CD and LC-CD-VE can outperform bulk oil and Tween 80 stabilized emulsions in terms of UV light stability, storage stability, and bioaccessibility. This work could offer fresh perspectives on stabilizer alternatives for Pickering emulsion delivery systems.

The Efficacy and Safety of Different Targeted Drugs for the Treatment of Generalized Myasthenia Gravis: A Systematic Review and Bayesian Network Meta-analysis.

BACKGROUND: The treatment of generalized myasthenia gravis (gMG) has been transformed by the development and approval of new targeted therapies. This analysis aimed to rank and compare the new therapies for gMG using efficacy and safety data from randomized controlled trials (RCTs). METHODS: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov (up to November 2022) for RCTs of targeted drugs for gMG. We used a Bayesian random-effects network meta-analysis (NMA) model and a Markov chain Monte Carlo (MCMC) model for statistical analysis. The primary outcome was the change in quantitative myasthenia gravis score (QMGS) from baseline, while the secondary outcome was the risk ratio (RR) of adverse events (AEs) during treatment. The surface under the cumulative ranking curve (SUCRA) was used to rank these targeted drugs, with higher SUCRA values indicating better efficacy or lower likelihood of AEs. RESULTS: In total, 13 studies (872 subjects) were included in this analysis evaluating 10 targeted drugs (batoclimab, belimumab, CFZ533, eculizumab, efgartigimod, nipocalimab, rituximab, ravulizumab, rozanolixizumab, and zilucoplan). With regards to the primary outcome, batoclimab [standardized mean difference (SMD), - 1.61; 95% credible interval (CrI), - 2.78, - 0.43] significantly reduced QMGS in patients with gMG when compared with placebo and was ranked as the most efficacious drug. Ranked second and third were eculizumab (SMD, - 0.67; 95% CrI, 1.43, 0.01) and zilucoplan (SMD, - 0.54; 95% CrI, - 1.56, 0.46), respectively. Nipoclimab (SMD, - 0.02; 95% CrI, - 1.04, 1.00) had the worst efficacy and ranked last among all targeted drugs. In our study, except for batoclimab, there was no statistically significant difference in the reduction of patient QMGS for the remaining targeted agents compared with placebo. With regards to the secondary outcomes, only batoclimab (RR, 0.19; 95% CrI, 0, 0.97) led to a significant reduction in the incidence of AEs when compared with the placebo. Belimumab (RR, 0.85; 95% CrI, 0.57, 1.19), CFZ533 (RR, 0.95; 95% CrI, 0.72, 1.25), eculizumab (RR, 0.99; 95% CrI, 0.85, 1.21), and efgartigimod (RR, 0.93; 95% CrI, 0.76, 1.15) also led to a lower incidence of AEs, although these effects were not significantly different from the placebo. CONCLUSIONS: Batoclimab had the best efficacy and safety for the treatment of gMG and was ranked first out of the 10 targeted drugs included in this study. Eculizumab was ranked second, and nipocalimab had the worst efficacy. With the exception of batoclimab, the incidence of AEs for the remaining drugs was not statistically significantly different from placebo. We note, however, that wide CrIs reflect the uncertainty in this analysis owing to the small number of available studies and low numbers of study participants; moreover, batoclimab had the widest CrI of all drugs in this analysis. More well-designed studies with long-term follow-up are needed to further evaluate and compare the efficacy and safety of these drugs in the future.

Neural specialization with generalizable representations underlies children's cognitive development of attention.

From childhood to adulthood, the human brain develops highly specialized yet interacting neural modules that give rise to nuanced attention and other cognitive functions. Each module can specialize over development to support specific functions, yet also coexist in multiple neurobiological modes to support distinct processes. Advances in cognitive neuroscience have conceptualized human attention as a set of cognitive processes anchored in highly specialized yet interacting neural systems. The underlying mechanisms of how these systems interplay to support children's cognitive development of multiple attention processes remain unknown. Leveraging developmental functional magnetic resonance imaging with attention network test paradigm, we demonstrate differential neurocognitive development of three core attentional processes from childhood to adulthood, with alerting reaching adult-like level earlier, followed by orienting and executive attention with more protracted development throughout middle and late childhood. Relative to adults, young children exhibit immature specialization with less pronounced dissociation of neural systems specific to each attentional process. Children manifest adult-like distributed representations in the ventral attention and cingulo-opercular networks, but less stable and weaker generalizable representations across multiple processes in the dorsal attention network. Our findings provide insights into the functional specialization and generalization of neural representations scaffolding cognitive development of core attentional processes from childhood to adulthood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Combination Immunotherapy of Oncolytic Flu-Vectored Virus and Programmed Cell Death 1 Blockade Enhances Antitumor Activity in Hepatocellular Carcinoma.

Oncolytic viruses (OVs) are appealing anti-tumor agents. But it is limited in its effectiveness. In this study, we used combination therapy with immune checkpoint inhibitor to enhance the antitumor efficacy of OVs. Using reverse genetics technology, we rescued an oncolytic influenza virus with the name delNS1-GM-CSF from the virus. After identifying the hemagglutination and 50% tissue culture infectivedose (TCID50) of delNS1-GM-CSF, it was purified, and the viral morphology was observed under electron microscopy. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) was used to identify the level of GM-CSF expression in delNS1-GM-CSF, and the GM-CSF expression level was determined after infection with delNS1-GM-CSF by enzyme linked immunosorbent assay (ELISA). To study the tumor-killing effect of delNS1-GM-CSF, we utilized the hepatocellular carcinoma (HCC) tumor-bearing mouse model. To examine signaling pathways, we performed transcriptome sequencing on mouse tumor tissue and applied western blotting to confirm the results. Changes in T-cell infiltration in HCC tumors following treatment were analyzed using flow cytometry and immunohistochemistry. DelNS1-GM-CSF can target and kill HCCs without damaging normal hepatocytes. DelNS1-GM-CSF combined with programmed cell death 1 blockade therapy enhanced anti-tumor effects and significantly improved mouse survival. Further, we found that combination therapy had an antitumor impact via the janus kinase-signal transducer and activator of transcription (JAK2-STAT3) pathway as well as activated CD4+ and CD8+T cells. Interestingly, combined therapy also showed promising efficacy in distant tumors. DelNS1-GM-CSF is well targeted. Mechanistic investigation revealed that it functions through the JAK2-STAT3 pathway. Combination immunotherapies expected to be a novel strategy for HCC immunotherapy.

Unlocking the Promise of Decellularized Pancreatic Tissue: A Novel Approach to Support Angiogenesis in Engineered Tissue.

Advancements in regenerative medicine have highlighted the potential of decellularized extracellular matrix (ECM) as a scaffold for organ bioengineering. Although the potential of ECM in major organ systems is well-recognized, studies focusing on the angiogenic effects of pancreatic ECM are limited. This study investigates the capabilities of pancreatic ECM, particularly its role in promoting angiogenesis. Using a Triton-X-100 solution, porcine pancreas was successfully decellularized, resulting in a significant reduction in DNA content (97.1% removal) while preserving key pancreatic ECM components. A three-dimensional ECM hydrogel was then created from this decellularized tissue and used for cell culture. Biocompatibility tests demonstrated enhanced adhesion and proliferation of mouse embryonic stem cell-derived endothelial cells (mES-ECs) and human umbilical vein endothelial cells (HUVECs) in this hydrogel compared to conventional scaffolds. The angiogenic potential was evaluated through tube formation assays, wherein the cells showed superior tube formation capabilities in ECM hydrogel compared to rat tail collagen. The RT-PCR analysis further confirmed the upregulation of pro-angiogenic genes in HUVECs cultured within the ECM hydrogel. Specifically, HUVECs cultured in the ECM hydrogel exhibited a significant upregulation in the expression of MMP2, VEGF and PAR-1, compared to those cultured in collagen hydrogel or in a monolayer condition. The identification of ECM proteins, specifically PRSS2 and Decorin, further supports the efficacy of pancreatic ECM hydrogel as an angiogenic scaffold. These findings highlight the therapeutic promise of pancreatic ECM hydrogel as a candidate for vascularized tissue engineering application.

Injectable Peptide Hydrogels Loaded with Murine Embryonic Stem Cells Relieve Ischemia In Vivo after Myocardial Infarction.

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide, especially in aging and metabolically unhealthy populations. A major target of regenerative tissue engineering is the restoration of viable cardiomyocytes to preserve cardiac function and circumvent the progression to heart failure post-MI. Amelioration of ischemia is a crucial component of such restorative strategies. Angiogenic ß-sheet peptides can self-assemble into thixotropic nanofibrous hydrogels. These syringe aspiratable cytocompatible gels were loaded with stem cells and showed excellent cytocompatibility and minimal impact on the storage and loss moduli of hydrogels. Gels with and without cells were delivered into the myocardium of a mouse MI model (LAD ligation). Cardiac function and tissue remodeling were evaluated up to 4 weeks in vivo. Injectable peptide hydrogels synergized with loaded murine embryonic stem cells to demonstrate enhanced survival after intracardiac delivery during the acute phase post-MI, especially at 7 days. This approach shows promise for post-MI treatment and potentially functional cardiac tissue regeneration and warrants large-scale animal testing prior to clinical translation.

Extraction and characterization of polysaccharides from Schisandra sphenanthera fruit by Lactobacillus plantarum CICC 23121-assisted fermentation.

Improving the yield of polysaccharides extracted from Schisandra sphenanthera is a major challenge in traditional Chinese medicinal plants. In this study, we investigated the potential of Lactobacillus plantarum CICC 23121-assisted fermentation as an extraction tool for S. sphenanthera polysaccharides (SSP). We observed that 11.12 ± 0.28 % of polysaccharides were extracted from S. sphenanthera using strain CICC 23121 -assisted fermentation (F-SSP), which was 53.38 % higher than that using hot water extraction (NF-SSP). The optimized parameters were a fermentation time of 15.5 h, substrate concentration of 4 %, and inoculum size of 3 %. Lactic acid produced by strain CICC 23121 increased the release of intracellular polysaccharides by breaking down cell walls. Compared to NF-SSP, F-SSP contained higher and lower total carbohydrate and protein contents, respectively, and its monosaccharide composition was the same as that of NF-SSP; however, their distributions were different. F-SSP had a higher molecular weight, better aqueous stability, and looser surface morphology, and strain CICC 23121-assisted fermentation did not change the molecular structure of SSP. Both NF-SSP and F-SSP showed the potential to regulate human intestinal microflora. Our findings revealed that strain CICC 23121-assisted fermentation is an efficient method for extracting S. sphenanthera polysaccharides without affecting their physicochemical and bioactive properties.

Development of the triadic neural systems involved in risky decision-making during childhood.

Risk-taking often occurs in childhood as a compex outcome influenced by individual, family, and social factors. The ability to govern risky decision-making in a balanced manner is a hallmark of the integrity of cognitive and affective development from childhood to adulthood. The Triadic Neural Systems Model posits that the nuanced coordination of motivational approach, avoidance and prefrontal control systems is crucial to regulate adaptive risk-taking and related behaviors. Although widely studied in adolescence and adulthood, how these systems develop in childhood remains elusive. Here, we show heterogenous age-related differences in the triadic neural systems involved in risky decision-making in 218 school-age children relative to 80 young adults. Children were generally less reward-seeking and less risk-taking than adults, and exhibited gradual increases in risk-taking behaviors from 6 to 12 years-old, which are associated with age-related differences in brain activation patterns underlying reward and risk processing. In comparison to adults, children exhibited weaker activation in control-related prefrontal systems, but stronger activation in reward-related striatal systems. Network analyses revealed that children showed greater reward-related functional connectivity within and between the triadic systems. Our findings support an immature and unbalanced developmental view of the core neurocognitive systems involved in risky decision-making and related behaviors in middle to late childhood.

Atypical child-parent neural synchrony is linked to negative family emotional climate and children's psychopathological symptoms.

[Correction Notice: An Erratum for this article was reported in Vol 79(2) of American Psychologist (see record 2024-62662-005). In the article "Atypical Child-Parent Neural Synchrony Is Linked to Negative Family Emotional Climate and Children's Psychopathological Symptoms," by Haowen Su, Christina B. Young, Zhuo Rachel Han, Jianjie Xu, Bingsen Xiong, Zisen Zhou, Jingyi Wang, Lei Hao, Zhi Yang, Gang Chen, and Shaozheng Qin (American Psychologist, 2024, Vol. 79, No. 2, pp. 210-224, https://doi.org/10.1037/amp0001173), Figure 2 and its caption were corrected to fix a mismatch between the r coefficients and scatterplots. The caption was changed from "(c) Child-parent hippocampal activity concordance was significantly higher for boundary than nonboundary event time series (Z = 2.30, p = .01). (d) Child-parent vmPFC activity concordance was marginally significantly higher for boundary than nonboundary time series (Z = -1.39, p = .08)" to "(c) Child-parent vmPFC activity concordance was marginally significantly lower for boundary than nonboundary time series (Z = -1.39, p = .08). (d) Child- parent hippocampal activity concordance was significantly higher for boundary than nonboundary event time series (Z = 2.30, p = .01)." In addition, in the second sentence of the second paragraph of the "Reduced Child-Parent vmPFC Connectivity With the Hippocampus Links to Negative Family Emotional Climate and Children's Internalizing Symptoms" section, "anxious/depressed" and "internalizing" were switched. All versions of this article have been corrected.] Family emotional climate is fundamental to children's well-being and mental health. Family environments filled with negative emotions may lead to increased psychopathological symptoms in the child through dysfunctional child-parent interactions. Single-brain paradigms have uncovered changes in brain systems and networks related to negative family environments, but how the neurobiological reciprocity between child and parent brains is associated with children's psychopathological symptoms remains unknown. Here, we first investigated the relation between family emotional climate and children's psychopathological symptoms in 395 child-parent dyads. Using a naturalistic movie-watching functional magnetic resonance imaging technique in a subsample of 50 child-parent dyads, we further investigated the neurobiological underpinnings of how family emotional climates are associated with children's psychopathological symptoms through child-parent neural synchrony. Children from negative family emotional climate experienced significantly more severe psychopathological symptoms. In comparison to child-stranger dyads, child-parent dyads exhibited higher intersubject correlations in the dorsal and ventral portions of the medial prefrontal cortex (mPFC), and greater concordance of activity with widespread regions critical for socioemotional skills. Critically, negative family emotional climate was associated with decreased intersubject functional correlation between the ventral-mPFC and the hippocampus during movie watching in child-parent dyads, which further accounted for higher children's internalizing symptoms. Together, our findings provide insights into the neurobiological mechanisms that negative family environments can cause and maintain psychopathological symptoms in children through atypical child-parent neural synchrony. This has important implications for a better understanding of how child-parent connections may mediate the relation between environmental risks and developmental outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Unraveling plant adaptation to nitrogen limitation from enzyme stoichiometry aspect in Karst soils: a case study of Rhododendron Pudingense.

Enzyme stoichiometry can reflect the resource limitation of soil microbial metabolism, and research on the relationships between plants and resource limitation in Karst Microhabitats is scarcely investigated. To clarify the extracellular enzyme stoichiometry characteristics in soil across different karst microhabitats and how the Rhododendron pudingense adapts to nutrient restrictions, plot investigation experiments were set up in Zhenning County, Qinglong County, and Wangmo County of Guizhou Province which included total three karst microhabitats, i.e., soil surface (SS), rock gully (RG), and rock surface (RS), by analyzing he rhizosphere soil nutrient, extracellular enzyme activity, and nutrient content of R. pudingense. The findings indicated that all karst microenvironments experienced varying levels of nitrogen (N) limitation, with the order of N limitation being as follows: SS > RG > RS. Notably, there were significant discrepancies in N content among different plant organs (p< 0.05), with the sequence of N content as follows: leaf > stem > root. However, no significant differences were observed in nutrient content within the same organ across different microenvironments (p > 0.05). A noteworthy discovery was the significant allometric growth relationship between C-P in various organs (p< 0.05), while roots and stems exhibited a significant allometric growth relationship between N-P (p< 0.05). The study highlighted the substantial impact of Total Nitrogen (TN) and N-acquiring enzymes (NAE) on nutrient allocation within the components of R. pudingense. Overall, the research demonstrated that N was the primary limiting factor in the study area's soil, and R. pudingense's nutrient allocation strategy was closely associated with N limitations in the karst microenvironment. Specifically, the plant prioritized allocating its limited N resources to its leaves, ensuring its survival. This investigation provided valuable insights into how plants adapt to nutrient restrictions and offered a deeper understanding of soil-plant interactions in karst ecosystems.

Differential Interventional Effects of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on High Fat Diet-Induced Obesity and Hepatic Pathology.

Current Dietary Guidelines for Americans recommend replacing saturated fat (SFA) intake with polyunsaturated fatty acids (PUFAs) and monosaturated fatty acids (MUFAs) but do not specify the type of PUFAs, which consist of two functionally distinct classes: omega-6 (n-6) and omega-3 (n-3) PUFAs. Given that modern Western diets are already rich in n-6 PUFAs and the risk of chronic disease remains high today, we hypothesized that increased intake of n-3 PUFAs, rather than n-6 PUFAs, would be a beneficial intervention against obesity and related liver diseases caused by high-fat diets. To test this hypothesis, we fed C57BL/6J mice with a high-fat diet (HF) for 10 weeks to induce obesity, then divided the obese mice into three groups and continued feeding for another 10 weeks with one of the following three diets: HF, HF+n-6 (substituted half of SFA with n-6 PUFAs), and HF+n-3 (substituted half of SFA with n-3 PUFAs), followed by assessment of body weight, fat mass, insulin sensitivity, hepatic pathology, and lipogenesis. Interestingly, we found that the HF+n-6 group, like the HF group, had a continuous increase in body weight and fat mass, while the HF+n-3 group had a significant decrease in body weight and fat mass, although all groups had the same calorie intake. Accordingly, insulin resistance and fatty liver pathology (steatosis and fat levels) were evident in the HF+n-6 and HF groups but barely seen in the HF+n-3 group. Furthermore, the expression of lipogenesis-related genes in the liver was upregulated in the HF+n-6 group but downregulated in the HF+n-3 group. Our findings demonstrate that n-6 PUFAs and n-3 PUFAs have differential effects on obesity and fatty liver disease and highlight the importance of increasing n-3 PUFAs and reducing n-6 PUFAs (balancing the n-6/n-3 ratio) in clinical interventions and dietary guidelines for the management of obesity and related diseases.

The low ratio of ghrelin in plasma and cerebrospinal fluid might be beneficial to sleep.

OBJECTIVE: Ghrelin is physiologically important for maintaining sleep rhythm. Cigarette smoking has been demonstrated to significantly increase the risk of insufficient sleep by regulating ghrelin at the central and peripheral levels. No research has been published to study the relationship between active smoking and sleep via ghrelin level in cerebrospinal fluid (CSF). METHODS: A total of 139 Chinese males were recruited and divided into active smokers (n = 77) and non-smokers (n = 62). The levels of CSF and plasma ghrelin were measured. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep. RESULTS: Non-smokers had lower PSQI scores (1.71 ± 1.93) than active smokers (3.70 ± 1.78). Non-smokers have significantly lower plasma ghrelin levels and lower plasma/CSF ghrelin ratio but higher CSF ghrelin than active smokers. Among non-smokers, plasma ghrelin levels were not correlated with PSQI scores (all p > 0.05), CSF ghrelin levels were positively correlated with PSQI scores (r = 0.309, p = 0.019), and the plasma/CSF ghrelin ratio was negatively correlated with PSQI scores (r = -0.346, p = 0.008). CONCLUSIONS: This study is the first to reveal the relationship between cigarette smoking, high CSF ghrelin levels and insufficient sleep, suggesting that maintaining a normal plasma/CSF ghrelin ratio may be the physiological mechanism of healthy sleep, and the insufficient sleep population must quit smoking.

Functional physical training improves fitness and cognitive development in 4~5 years old children.

Background: Development of physical and cognitive function is very critical in 4~5 years children. It has been addressed in this research if the 18 weeks of specific functional training with or without cognitive training can be effective on improving fitness and cognitive development in 4~5 years preschool children. Methods: A total of 126 preschool children in the 4~5 age range were selected as participants and randomly assigned to one of four groups: the control group (C), the functional physical training group (P), the cognitive training group (CT), and the functional physical training combined with cognitive training group (PCT). Results: The results revealed significant pre/post differences in body height and weight among all four groups of children. Furthermore, there was no significant difference in physical fitness between the C group and the CT group after the intervention. However, the children in the P group and the PCT group showed significant improvements in three indicators including standing long jump, continuous jump, and 10-meter shuttle running. Additionally, the children in P group, CT group, and the PCT group demonstrated significant improvement in simple reaction time, attention, and spatial memory. No significant cognitive improvement was found in C group. Conclusion: Functional physical training with or without cognitive intervention can promote both physical fitness and cognitive development in children aged 4~5 years. Cognitive training alone can significantly improve cognitive function but not physical. Therefore, functional physical training can be used alone to improve the physical and cognitive abilities for aged 4~5 years old children.

Connectome-based modeling reveals a resting-state functional network that mediates the relationship between social rejection and rumination.

Background: Rumination impedes problem solving and is one of the most important factors in the onset and maintenance of multiple psychiatric disorders. The current study aims to investigate the impact of social rejection on rumination and explore the underlying neural mechanisms involved in this process. Methods: We utilized psychological questionnaire and resting-state brain imaging data from a sample of 560 individuals. The predictive model for rumination scores was constructed using resting-state functional connectivity data through connectome-based predictive modeling. Additionally, a mediation analysis was conducted to investigate the mediating role of the prediction network in the relationship between social rejection and rumination. Results: A positive correlation between social rejection and rumination was found. We obtained the prediction model of rumination and found that the strongest contributions came from the intra- and internetwork connectivity within the default mode network (DMN), dorsal attention network (DAN), frontoparietal control network (FPCN), and sensorimotor networks (SMN). Analysis of node strength revealed the significance of the supramarginal gyrus (SMG) and angular gyrus (AG) as key nodes in the prediction model. In addition, mediation analysis showed that the strength of the prediction network mediated the relationship between social rejection and rumination. Conclusion: The findings highlight the crucial role of functional connections among the DMN, DAN, FPCN, and SMN in linking social rejection and rumination, particular in brain regions implicated in social cognition and emotion, namely the SMG and AG regions. These results enhance our understanding of the consequences of social rejection and provide insights for novel intervention strategies targeting rumination.

Integrating Network Pharmacology and Experimental Validation to Decipher the Anti-Inflammatory Effects of Magnolol on LPS-induced RAW264.7 Cells.

INTRODUCTION: Magnolol is beneficial against inflammation-mediated damage. However, the underlying mechanisms by which m+agnolol exerts anti-inflammatory effects on macrophages remain unclear. OBJECTIVE: In this study, network pharmacology and experimental validation were used to assess the effect of magnolol on inflammation caused by lipopolysaccharide (LPS) in RAW264.7 cells. MATERIALS AND METHODS: Genes related to magnolol were identified in the PubChem and Swiss Target Prediction databases, and gene information about macrophage polarization was retrieved from the GeneCards, OMIM, and PharmGKB databases. Analysis of protein-protein interactions was performed with STRING, and Cytoscape was used to construct a component-target-disease network. GO and KEGG enrichment analyses were performed to ascertain significant molecular biological processes and signaling pathways. LPS was used to construct the inflammatory cell model. ELISA and qRT‒PCR were used to examine the expression levels of inflammationassociated factors, immunofluorescence was used to examine macrophage markers (CD86 and CD206), and western blotting was used to examine protein expression levels. RESULTS: The hub target genes of magnolol that act on macrophage polarization were MDM2, MMP9, IL-6, TNF, EGFR, AKT1, and ERBB2. The experimental validation results showed that magnolol treatment decreased the levels of proinflammatory factors (TNF-α, IL-1ß, and IL-6). Moreover, the levels of anti-inflammatory factors (IL-10 and IL-4) were increased. In addition, magnolol upregulated the expression of M2 markers (Agr-1, Fizzl, and CD206) and downregulated M1 markers (CD86). The cell experiment results supported the network pharmacological results and demonstrated that magnolol alleviated inflammation by modulating the PI3k-Akt and P62/keap1/Nrf2 signaling pathways. CONCLUSION: According to network pharmacology and experimental validation, magnolol attenuated inflammation in LPS-induced RAW264.7 cells mainly by inhibiting M1 polarization and enhancing M2 polarization by activating the PI3K/Akt and P62/keap1/Nrf2 signaling pathways.

Knowledge structure and emerging trends of cognitive impairment induced by sleep deprivation: A bibliometric analysis based on CiteSpace and VOSviewer from 2000 to 2022.

This paper implements a bibliometric approach to investigate the research hotspots and future research directions in the relevant field literature. It also offers research ideas and methods for preventing and treating cognitive impairment induced by sleep deprivation in the clinical setting. The evolution of various clusters in the field is summarized through Citespace's projection function for keywords in the literature. CiteSpace and Vosviewer are utilized to analyze and visualize the attributes of the articles, including number of publications, citation frequency, country/region, institution, journal, authors, keywords, and references, from the 2280 publications obtained. A total of 2280 publications were collected, with the number of papers and citations in the field continuously increasing year by year. The most influential country in this field is the United States, and the University of Washington is the most influential institution. The most authoritative journal in the field is identified as SLEEP. Sleep deprivation, prefrontal cortex, and performance are the current topics of interest. The article with the strongest citation burst, lasting from 2015 to 2018, is "Sleep Drives Metabolite Clearance from the Adult Brain." The most influential article and co-cited reference, "Neurocognitive Consequences of Sleep Deprivation," highlights that sleep deprivation from various causes may lead to cognitive impairment. Future research should investigate all forms of cognitive impairment resulting from sleep deprivation. The findings of this study will assist researchers in improving their knowledge structure, identifying research hotspots, and revealing future directions in the field.

HAHNet: a convolutional neural network for HER2 status classification of breast cancer.

OBJECTIVE: Breast cancer is a significant health issue for women, and human epidermal growth factor receptor-2 (HER2) plays a crucial role as a vital prognostic and predictive factor. The HER2 status is essential for formulating effective treatment plans for breast cancer. However, the assessment of HER2 status using immunohistochemistry (IHC) is time-consuming and costly. Existing computational methods for evaluating HER2 status have limitations and lack sufficient accuracy. Therefore, there is an urgent need for an improved computational method to better assess HER2 status, which holds significant importance in saving lives and alleviating the burden on pathologists. RESULTS: This paper analyzes the characteristics of histological images of breast cancer and proposes a neural network model named HAHNet that combines multi-scale features with attention mechanisms for HER2 status classification. HAHNet directly classifies the HER2 status from hematoxylin and eosin (H&E) stained histological images, reducing additional costs. It achieves superior performance compared to other computational methods. CONCLUSIONS: According to our experimental results, the proposed HAHNet achieved high performance in classifying the HER2 status of breast cancer using only H&E stained samples. It can be applied in case classification, benefiting the work of pathologists and potentially helping more breast cancer patients.